As a general alpha2 adrenergic antagonist, yohimbine has been widely used for research needs and in the therapy of malfunction of the noradrenergic system. In this study we analysed the effects of iontophoretically applied yohimbine on 79 prefrontal cortical (PFC) neurons of the rat in vivo. Our results indicate the inhibitory effect of norepinephrine on PFC neurons, which was simulated by yohimbine. The effect of yohimbine was not blocked by known alpha1 or postsynaptic alpha2 receptor agents. These results indicate that yohimbine exerts its antagonising and hyperpolarising effect on presynaptic rather than postsynaptic alpha2 receptors. Since these receptors have a permissive role in maintaining neural activity, their malfunction may contribute to the behavioural deficits observed in prefrontal disorders.